Electroacupuncture Modulation of Chondroitin Sulfate Glycosaminoglycan Promotes the Repair of Damaged Spinal Cord in Rats.

Abstract

BACKGROUND: The perineuronal net (PNN) is an important extracellular environment around parvalbumin interneuron (PV IN) in the spinal cord. Chondroitin sulfate proteoglycan (CSPG) serves as a key factor mediating PNN effects on the spinal cord, primarily formed by covalently linked chondroitin sulfate glycosaminoglycan (CS-GAG) chains and diverse core proteins. Extensive research suggests that degradation of CS-GAG following nerve injury may contribute to severe spinal cord damage. Inhibiting CS-GAG degradation could enhance PNN stability and plasticity, thereby promoting recovery from nerve injury. Electroacupuncture (EA) intervention demonstrates significant neuroprotective effects, facilitating restoration of spinal cord nerve function and axonal regeneration. This study aims to observe the changes in CS-GAG and the expression of PV IN after spinal cord injury (SCI) in rats and explore the effect. METHODS: An SCI model was established in Sprague-Dawley rats using an Infinite Horizon (IH) impactor, and EA was applied to the Jia-ji acupoints (EX-B2). The Basso-Beattie-Bresnahan (BBB) score of SCI rats was evaluated, and electromyography (EMG) of the gastrocnemius muscle of the hind limbs was performed. The protein expression levels of CS-GAG and glutamic acid decarboxylase (GAD) were detected using western blotting, and perineuronal nets (PNN) and PV IN were observed using immunofluorescence (IF). Fiber-optic calcium imaging was used to detect and analyze PV IN activity. Adeno-associated virus containing carbohydrate sulfotransferase 11 (Chst11) was injected into T9 and T10 spinal cord spaces using a microneedle, and changes in CS-GAG in the spinal cord of SCI rats before and after EA intervention were observed. RESULTS: CS-GAG and GAD expression levels were significantly decreased after SCI and PNN stability was reduced. Chondroitinase ABC (ChABC) treatment increased PV IN activity and GAD expression. EA effectively promoted an increase in CS-GAG and GAD, improved PNN stability and PV IN activity, and reversed the inhibitory effect of Chst11, thereby facilitating the rehabilitation of rats with SCI. CONCLUSION: The mechanisms and effects of EA on SCI repair were investigated. The results revealed that EA can regulate the recovery of PNN structure and function via CS-GAG and GAD, improve PV IN activity, and reverse the inhibitory effect of Chst11 to promote SCI rehabilitation in rats.